Previous studies have demonstrated that P. falciparum malaria infections develop more slowly in individuals with G-6-PD deficiency and thalassemia. In vitro culture studies offer direct evidence that the rate of parasite multiplication is inhibited in erythrocytes from individuals with these genetic disorders. As these erythrocytes are sensitive to oxidant damage and there is considerable evidence that the parasite may impart an oxidant stress upon the infected red cell, we proposed that the redox status of the infected erythrocyte is an important determinant of parasite multiplication. We have shown that this may occur because the parasite utilizes NADPH generated in the pentose shunt of the erythrocyte resulting in competition for this substrate in the infected cell. This would make the red cell sensitive to oxidant damage because NADPH is required for the reduction of glutathione which is necessary for detoxification of oxidants generated within the erythrocyte. The studies outlined in this proposal will better define the redox status of P. falciparum infected normal, G-6-PD deficient, and thalassemic red cells cultivated in vitro by the technique of Trager and Jensen. We will compare methemogloblin levels, H2O2 generation, GSH stability, GSH regeneration, and lipid peroxidation in the three cell types. The effects of oxidant stress on culture cells will be assessed by measuring these parameters after exposure to oxidants and anti-oxidants. The enzyme glutamate dehydrogenase has been suggested as an important source of NADPH for the parasite. We will determine the role of this enzyme in maintenance of GSH within the infected abnormal erythrocytes. Finally, the contribution of de novo synthesis of GSH in protecting the infected erythrocyte against parasite induced oxidant damage will be determined. Malaria continues to be a major World health problem and is, in fact, increasing in frequency. There is little understanding of the biochemical interactions between host and parasite. By studying the redox status of infected normal and abnormal erythrocytes, we hope to add to this understanding. Finally, as in vitro malaria culture may be dependent on the redox status of the red cell, these studies may provide insights which lead to development of better culture techniques needed for vaccine production.